Lakatos Szandra, Rosta Judit
Department of Physiology, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary.
Int J Mol Sci. 2025 Aug 5;26(15):7556. doi: 10.3390/ijms26157556.
Microglia, the brain's resident innate immune cells, play a fundamental role in maintaining neural homeostasis and mediating responses to injury or infection. Upon activation, microglia undergo morphological and functional changes, including phenotypic switching between pro- and anti-inflammatory types and the release of different inflammatory mediators. These processes contribute to neuroprotection and the pathogenesis of various central nervous system (CNS) disorders. Mast cells, although sparsely located in the brain, exert a significant influence on neuroinflammation through their interactions with microglia. Through degranulation and secretion of different mediators, mast cells disrupt the blood-brain barrier and modulate microglial responses, including alteration of microglial phenotypes. Notably, mast cell-derived factors, such as histamine, interleukins, and tryptase, activate microglia through various pathways including protease-activated receptor 2 and purinergic receptors. These interactions amplify inflammatory cascades via various signaling pathways. Previous studies have revealed an exceedingly complex crosstalk between mast cells and microglia suggesting a bidirectional regulation of CNS immunity, implicating their cooperation in both neurodegenerative progression and repair mechanisms. Here, we review some of the diverse communication pathways involved in this complex interplay. Understanding this crosstalk may offer novel insights into the cellular dynamics of neuroinflammation and highlight potential therapeutic targets for a variety of CNS disorders.
小胶质细胞是大脑中固有的先天性免疫细胞，在维持神经稳态以及介导对损伤或感染的反应中发挥着重要作用。激活后，小胶质细胞会发生形态和功能变化，包括促炎型和抗炎型之间的表型转换以及释放不同的炎症介质。这些过程有助于神经保护以及各种中枢神经系统（CNS）疾病的发病机制。肥大细胞虽然在大脑中分布稀疏，但通过与小胶质细胞的相互作用对神经炎症产生重大影响。通过脱颗粒和分泌不同的介质，肥大细胞破坏血脑屏障并调节小胶质细胞反应，包括改变小胶质细胞表型。值得注意的是，肥大细胞衍生的因子，如组胺、白细胞介素和类胰蛋白酶，通过包括蛋白酶激活受体2和嘌呤能受体在内的各种途径激活小胶质细胞。这些相互作用通过各种信号通路放大炎症级联反应。先前的研究揭示了肥大细胞和小胶质细胞之间极其复杂的相互作用，表明中枢神经系统免疫存在双向调节，这意味着它们在神经退行性进展和修复机制中都有合作。在此，我们回顾了参与这种复杂相互作用的一些不同的通信途径。了解这种相互作用可能为神经炎症的细胞动力学提供新的见解，并突出各种中枢神经系统疾病的潜在治疗靶点。
